Abstract

We reported that cancer patients treated by anthracycline-based or nonanthracycline chemotherapy developed an early impairment of myocardial relaxation at echocardiography or persistent elevations of the cardiac hormone, B-type natriuretic peptide (BNP). Post hoc pharmacologic analyses showed that BNP elevations were induced by impaired relaxation and caused positive lusitropic effects that maintained a normal relaxation. High BNP and impaired relaxation were therefore characterized as mutually exclusive manifestations of diastolic dysfunction but high BNP caused positive chronotropism and inappropriate tachycardia. Some patients developed increased circulating levels of cardiac troponin I isoform (cTnI), marker of cardiomyocyte necrosis. Here we characterized whether cTnI elevations correlated with diastolic dysfunction that manifested as impaired relaxation or high BNP. The effects of high BNP on cTnI elevations were also characterized. We show that impaired relaxation or high BNP were significantly more frequent for patients with cTnI elevations. High BNP diminished the plasma peak and area under curve of cTnI but this was accompanied by inappropriate tachycardia. cTnI elevations occurred only in patients treated by anthracyclines; moreover, the association of impaired relaxation or high BNP with cTnI elevations was significantly more frequent for doxorubicin as compared to its analogue, epirubicin. These findings describe cause-and-effect relations between impaired relaxation and cardiomyocyte necrosis, illuminate the role of anthracycline analogues, denote that beneficial effects of BNP on relieving impaired relaxation and cardiomyocyte necrosis are counterbalanced by inappropriate tachycardia. Patients showing troponin elevations and impaired relaxation or high BNP should be treated by lusitropic drugs that lack a positive chronotropism.